Zhuang Tong
Zhuang Tong Uses, Dosage, Side Effects, Food Interaction and all others data.
Zhuang Tong is an indole-based, hydrophobic, dual-acting direct antiviral/host-targeting agent used for the treatment and prophylaxis of influenza and other respiratory infections. It has been in use in Russia for approximately 25 years and in China since 2006. Its invention is credited to a collaboration between Russian scientists from several research institutes 40-50 years ago, and reports of its chemical synthesis date back to 1993. Zhuang Tong's ability to exert antiviral effects through multiple pathways has resulted in considerable investigation into its use for a variety of enveloped and non-enveloped RNA and DNA viruses, including Flavivirus, Zika virus, foot-and-mouth disease, Lassa virus, Ebola virus, herpes simplex,, hepatitis B and C viruses, chikungunya virus, reovirus, Hantaan virus, and coxsackie virus B5. This dual activity may also confer additional protection against viral resistance, as the development of resistance to umifenovir does not appear to be significant.
Zhuang Tong is currently being investigated as a potential treatment and prophylactic agent for COVID-19 caused by SARS-CoV2 infections in combination with both currently available and investigational HIV therapies.
Zhuang Tong exerts its antiviral effects via both direct-acting virucidal activity and by inhibiting one (or several) stage(s) of the viral life cycle. Its broad-spectrum of activity covers both enveloped and non-enveloped RNA and DNA viruses. It is relatively well-tolerated and possesses a large therapeutic window - weight-based doses up to 100-fold greater than those used in humans failed to produce any pathological changes in test animals.
| Trade Name | Zhuang Tong |
| Generic | Umifenovir |
| Umifenovir Other Names | Umifenovir |
| Type | |
| Formula | C22H25BrN2O3S |
| Weight | Average: 477.42 Monoisotopic: 476.076927 |
| Protein binding | Data regarding protein-binding of umifenovir are currently unavailable. |
| Groups | Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | China |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Zhuang Tong is a dual direct-acting antiviral/host-targeting agent used in the treatment and prophylaxis of influenza and other respiratory viruses.
Zhuang Tong is currently licensed in China and Russia for the prophylaxis and treatment of influenza and other respiratory viral infections. It has demonstrated activity against a number of viruses and has been investigated in the treatment of Flavivirus, Zika virus, foot-and-mouth disease, Lassa virus, Ebola virus, and herpes simplex. In addition, it has shown in vitro activity against hepatitis B and C viruses, chikungunya virus, reovirus, Hantaan virus, and coxsackie virus B5.
Zhuang Tong is currently being investigated as a potential treatment and prophylactic agent for the prevention of COVID-19 caused by SARS-CoV-2 infections.
How Zhuang Tong works
Zhuang Tong is considered both a direct-acting antiviral (DAA) due to direct virucidal effects and a host-targeting agent (HTA) due to effects on one or multiple stages of viral life cycle (e.g. attachment, internalization), and its broad-spectrum antiviral activity is thought to be due to this dual activity. It is a hydrophobic molecule capable of forming aromatic stacking interactions with certain amino acid residues (e.g. tyrosine, tryptophan), which contributes to its ability to directly act against viruses. Antiviral activity may also be due to interactions with aromatic residues within the viral glycoproteins involved in fusion and cellular recognition, with the plasma membrane to interfere with clathrin-mediated exocytosis and intracellular trafficking, or directly with the viral lipid envelope itself (in enveloped viruses). Interactions at the plasma membrane may also serve to stabilize it and prevent viral entry (e.g. stabilizing influenza hemagglutinin inhibits the fusion step necessary for viral entry).
Due to umifenovir’s ability to interact with both viral proteins and lipids, it may also interfere with later stages of the viral life cycle. Some virus families, such as Flaviviridae, replicate in a subcellular compartment called the membranous web - this web requires lipid-protein interactions that may be hindered by umifenovir. Similarly, viral assembly of hepatitis C viruses is contingent upon the assembly of lipoproteins, presenting another potential target.
Toxicity
The oral LD50 of umifenovir in mice and rats has been reported as 340-400 mg/kg and >3000 mg/kg, respectively. Chronic administration of doses 10-50 times the therapeutic human dose resulted in no pathological changes to animal subjects.
Further information regarding the management of umifenovir overdose is unavailable.
Food Interaction
No interactions found.Volume of Distribution
Data regarding the volume of distribution of umifenovir are currently unavailable.
Elimination Route
Zhuang Tong is rapidly absorbed following oral administration, with an estimated Tmax between 0.65-1.8 hours. The Cmax has been estimated as 415 - 467 ng/mL and appears to increase linearly with dose, and the AUC0-inf following oral administration has been estimated to be approximately 2200 ng/mL/h.
Half Life
The half-life of umifenovir following oral administration has been estimated to be between 17-21 hours. Serum half-lives of the M5, M6-1, and M8 metabolites were found to be 26.3 ± 5.9, 25.0 ± 5.4, and 25.7 ± 8.8, respectively.
Clearance
In a study involving healthy male Chinese volunteers, the oral clearance of umifenovir was found to be 99 ± 34 L/h.
Elimination Route
The major route of elimination is via the feces. Approximately 40% of an ingested dose is excreted unchanged, of which 38.9% is excreted in the bile and 0.12% excreted through the kidneys. The total recovery of parent drug and metabolites in the urine accounts for less than 1% of an ingested dose.
Innovators Monograph
You find simplified version here Zhuang Tong
